Another study of Medtronic Inc.’s Infuse Bone Graft product that involved soldiers at Walter Reed Army Medical Center is coming under fire. According to a report in the Minneapolis Star Tribune, Dr. Charles Rosen, president of the Association for Medical Ethics, has written a letter to the U.S. Army Surgeon General expressing concerns about the way the Medtronic Infuse study was conducted.

Infuse Bone Graft, which is manufactured by Medtronic., contains recombinant human Bone Morphogenetic Protein (rhBMP-2), a protein released naturally by the body. It is approved to treat a spinal condition called Degenerative Disc Disease, as well as open fractures of the tibia. It is also approved for use in two dental bone grafting procedures: sinus augmentation and localized alveolar ridge augmentation.

In July 2008, the Food & Drug Administration (FDA) warned that the use of Infuse Bone Graft and similar products had caused serious problems when they were used off-label in cervical spine (neck) surgeries. Patients reported difficulty swallowing, breathing and speaking. Several required emergency treatment, including tracheotomies and the insertion of feeding tubes, as well as second surgeries.

According to the Star Tribune, the Infuse study questioned by Dr. Rosen involved its use in procedures that at the time were not approved by the FDA. Doctors are allowed to used approved medical devices in this way – a practice known as off-label use. However, medical firms are barred from promoting off-label uses.

The Walter Reed Infuse study detailed by the Star Tribune was conducted by Dr. David Polly. We reported in August that Dr. Polly had resigned from the board of the American Academy of Orthopaedic Surgeons after he was criticized for not disclosing his financial relationship with Medtronic when he testified before a Senate committee in 2006 urging more funding for research into combat-related injuries. According to Minneapolis-St. Paul Business Journal, Polly never told the panel that he was a Medtronic consultant, and was billing the company $6,000 for his appearance. Following his May 2006 testimony, Polly and his colleagues at the University of Minnesota received a $466,644 Department of Defense grant for a two-year study involving Infuse Bone Graft.

According to the Minneapolis Star Tribune, the Walter Reed study involved 35 patients with back problems who were treated with Infuse packed into a bioabsorbable implant called Hydrosorb, which was distributed by Medtronic, and inserted between the vertebrae. The results of the study were subsequently published in a 2004 edition of the medical journal Neurosurgical Focus, the Star Tribune said. Dr. Polly was involved in 10 of the cases cited in the article, though at the time of the study, he was not a paid consultant for Medtronic.

When the study was conducted, Infuse had only been approved for single-level fusion surgeries in the lower back using a different type of supportive cage than Hydrosorb. According to the Star Tribune report, 14 of the patients in the Walter Reed study had multiple-level fusions, two of which involved fusing five spinal levels.

In his letter to the Army Surgeon General, Dr. Rosen asks if the patients in the Walter Reed study were given informed consent before spine surgery. Specifically, he asked if they knew the products used in their surgeries were not approved by the FDA. He also asks if an Institutional Review Board — an independent ethics board that oversees clinical studies — was engaged at Walter Reed “to oversee and approve this experiment on the men and women of the armed forces.” According to the Star Tribune, the Army Surgeon General, who has acknowledged receiving the letter, has not yet issued a formal reply.

An attorney for Dr. Polly told the Star Tribune that patients in the study where “properly informed of alternative treatments, as well as the risks and benefits of the surgery.” The attorney also asserted that they “were not part of any clinical trial or ‘experiment,’ as erroneously assumed by the person who wrote the letter.” Dr. Polly’s lawyer characterized the study as a “historical review of surgeries” and a ‘look-back inquiry.”

Incidentally, one of the co-author on Dr. Polly’s Walter Reed Infuse study was Dr. Timothy Kuklo. As we’ve reported previously, Dr. Kuklo has been accused of falsifying data in another Infuse study done at Walter Reed. That study claimed to show that wounded soldiersâ€™ leg injuries healed better when Infuse was used. But an Army investigation found several problems with it. For one thing, the study cited higher numbers of patients and injuries than Walter Reed officials could account for. Dr. Kuklo also did not obtain the Armyâ€™s required permission to conduct the study, and investigators at Walter Reed have also concluded that Kuklo forged his co-authors signatures on the study. Dr. Kukloâ€™s study was published in the Journal of Bone & Joint Surgery in August 2008, but retracted last March.

In June, Medtronic disclosed that over a ten year period, it had paid Dr. Kuklo roughly $850,000 in direct and direct payments. Between 2000 and 2006, he was paid to train other physicians in how to implant Medtronic products. In 2006, he signed on as a consultant for the company, a relationship which ended earlier this year. However, Medtronic has maintained that it had nothing to do with Dr. Kukloâ€™s Infuse study.

Dr. Kuklo left the Army and Walter Reed in 2006, and joined the faculty at Washington University Medical School in St. Louis. Dr. Kuklo resigned that position in August.